Michael McEntee, DVM, is an Associate Professor of Pathology at UT with Board Certification in Anatomic Veterinary Pathology. In addition to a 75% commitment to service and residency training at UT, he has been actively engaged in research involving mouse models of intestinal and pulmonary carcinogenesis. A reduction in service commitments made possible by a K26 award will allow Dr. McEntee to expand pathobiology research in the Apc(Min) mouse model of intestinal tumorigenesis, provide morphologic evaluation of mutant mice for the Life Sciences Division at ORNL, and originate phenotype analysis of mutant mice as a component of the Pathology Residency Training Program at the College of Veterinary Medicine. Dr. McEntee will commit a 35% to 40% effort in mouse research to: 1) examine the relationships between intestinal tumorigenesis, arachidonic acid (AA) and its metabolites; 2) determine the expression pattern of prostaglandin-E2 (PGE2) receptors in tumor tissues; and 3) characterize interactions between neoplastic and non-neoplastic cells in Apc(Min) mouse tumors. Planned experiments include in situ hybridization to detect gene expression, modification of the Apc(Min) mouse through transgenic cross- breeding experiments, and oral introduction of cDNA to effect protein expression in the intestinal tract. These are all new techniques for Dr. McEntee and applicable to future murine pathology research at UT. ORNL houses more than 350 strains of mutant mice and is only a 25 minute drive from the UT-Knoxville campus. The Life Sciences Division at ORNL continues to generate genetic mutants, is incorporated with UT and other Universities across Tennessee in the Tennessee Mouse Genome Consortium (TMGC) and urgently needs assistance with phenotypic analysis to determine gene-function relationships. Dr. McEntee will commit 10% to 15% effort to phenotypic evaluation of these mice and establishment of mutant mouse pathology as a component of the Department's Residency Training Program, preparing residents for careers involving genetically altered mice and facilitating future interactions between ORNL, the TMGC, UT faculty, residents and graduate students.